Project 3 entitled Experimental Animal Models and in vivo vaccine Evaluation studies, attempts to define several generic questions in the area of HIV vaccine development by studying the protective ability of a variety of subunit vaccines in nonhuman primate models of SIV and in selected instances of HIV-1. The SIV models has the ability to compare the immunogenicity and protection of subunit vaccines with that achieved by an attenuated live replicating virus and will be utilized in this project to do so. This project has been divided into two sections. Section A descries experiments to further develop the SIV and HIV-1 models as effective challenge models for defining protective immunity. We will design and test an SIV cell associated intra-rectal mucosal transmission model and further refine and SIV heterosexual transmission model that will closely mimic a natural mode of transmission in the human population. Section A will also conduct experiments in an HIV-1 M. nemestrina infection model development by inoculating M. nemestrina with HIV-1 MN and titrating an animal infectious dose for further vaccine challenge studies. Additionally, the HIV-1 M. nemestrina model will be used to test potential protection afforded by administration of anti-HIV- 1 immunoglobulin. Section B will use the SIV and HIV nonhuman primate models to demonstrate the in vivo immunogenicity and protection from challenge of the immunogens derived from vaccina virus recombinants expressing the env, gag, and pool or the combination of the three viral proteins (pseudovirions) from the two SIV isolates (SIVMne and SIVSmm/H-4 and two HIV-1 isolates, IIIB and MN).